The term “micro-fluidics” refers to technologies that involve the manipulation of very small amounts (typically nano-liter to micro-liter quantities) of liquids or gases. Micro-fluidic technologies are now used to carryout a variety of chemical and biological processes. Many benefits are realized by conducting these types of processes at the micro-scale. In short, there are things that can be done at the micro-scale that simply cannot be done, or cannot be done as quickly, cheaply, precisely, or as safely with macro-scale process configurations.
Micro-fluidic processes are usually conducted in a network of micro-channels. These micro-channels, which are typically only tens of microns deep and wide, are usually formed via lithographic processing and chemical etching. The network of channels is typically formed in a postage stamp-sized glass, polymer, or silicon substrate.
In addition to the network of micro-channels, some micro-fluidic systems include mixers, reservoirs, diffusion chambers, heaters, integrated electrodes, pumps, valves, and the like. The phrase “lab-on-a-chip” has been coined to refer to these integrated micro-fluidic systems, which are capable of conducting chemical reactions, high-throughput screening and drug discovery, DNA amplification in genomics, and cell screening, counting, and sorting and biochemical monitoring.
One important application for lab-on-a-chip is “capillary electrophoresis.” Using capillary electrophoresis, substances are separated on the basis of variations in the velocities of charged particles (i.e., electrophoretic mobility) in a conducting fluid as they migrate under the influence of an electric field. Capillary electrophoresis has successfully been employed in the analysis of DNA fragments and other bio-molecules. Using certain modifiers, it is even possible to separate neutral solutes.
FIG. 1A depicts an example of a typical capillary electrophoresis (“CE”) chip. The CE chip includes a network of micro-fluidic channels. In the example that is depicted in FIG. 1A, the network comprises a sample channel and a carrier channel. A sample of fluid to be tested is introduced into the network at one of the sample-channel reservoirs. The sample is usually added to the reservoirs via a syringe. The sample flows through the sample-channel via capillary action. A carrier, such as saline, glucose, etc., and usually a pH buffer are introduced into the network at one of the carrier-channel reservoirs.
A high voltage, usually in excess of few hundred volts and sometimes above thousand volts, is applied for a brief period (i.e., in the range of a few seconds to a few minutes) between the reservoirs via electrical probes. This induces an electro-osmotic flow, which is used to launch a small plug of the sample fluid into the carrier channel at the intersection of the two channels. The various charged species in the small sample will stratify in the carrier channel as a consequence of differences in electrophoretic mobility. At a certain location, the fluid in the carrier channel is interrogated (e.g., optically, electrically, etc.). Due to stratification, the various species will pass the detection location at different times. This provides a means for resolving the various species within the sample.
While the CE chip provides an efficient platform for conducting capillary electrophoresis, there are drawbacks associated with its use. In particular, little attention has been paid to fluid and power management; these resources are not efficiently integrated with the CE chip. Since sample and carrier fluids are manually added to the CE chip via syringes, the chip cannot be sealed. This presents a risk of contamination. Furthermore, the application of high voltage via external electrodes presents a safety hazard. Additionally, the prevailing ad-hoc approach to supplying fluid and power to the CE chip also raises concerns about the reproducibility of results. And, more generally, the current approach to capillary electrophoresis is so cumbersome and inconvenient that, notwithstanding its utility for any particular analysis application, there is a reluctance to use the technique.